This invention relates generally to a non-invasive method for treating dirofilaria immitis in canines and, more particularly, to a method for treating that stage of the disease caused by adult heartworms. Still further, the invention employs ivermectin--a composition hereto-fore unknown in the primary treatment of adult heartworms.
Heartworms are commonly found to reside in the right ventricle of a dog's heart and the adjacent blood vessels. Adult heartworms cause inflammation of the walls of the arteries in the lungs, obstruct blood vessels and interfere with the blood supply to vital organs. Common symptoms of adult heartworm disease in canines include low-grade nocturnal cough, distension of the limbs and lower abdomen and lethargy. Left Untreated, heartworm parasites can result in the death of the host canine and can be infectiously transmitted to other canines by way of numerous mosquito species which function as an intermediate host.
Dirofilaria immitis, the disease caused by parasitic adult heartworms in canines, is characterized by several developmental stages. Specifically, microfilariae are known to be deposited by female heartworms into the bloodstream of canines. The microfilariae develop further once ingested by a mosquito which functions as an intermediate host. Within the mosquito, microfilariae develop into infective larvae which, once a dog is bitten by the mosquito, migrate to the dog's heart where maturation into adult worms occurs.
As reported as early as January, 1963, the only known pathologic changes in canines based upon heartworm disease result from the direct or indirect effects of adult heartworms. No significant damage is done by either the microfilariae or the developing larvae. (See Jackson, Journal of the American Veterinary Medical Association 142, pages 23-26 (1963)). Accordingly, efforts in the treatment of heartworms in canines, since that time, have largely been directed toward destruction of the adult heartworm.
Destruction of the adult worm has been accomplished surgically and by chemotherapy. Beginning in the 1940's and continuing into the early 1960's several open-chest surgical techniques were developed and practiced for removing worms from the right ventricle and adjacent arteries. Surgical removal of worms through the animal's jugular vein was also practiced for some time and remains the recommended procedure for eliminating adult worms in confirmed cases of heartworm caval syndrome. With this exception, however, surgical treatments have yielded to chemotherapies because they proved expensive, risky (mortality rates in excess of 10% were reported) and, most importantly, non-efficacious. In fact, chemotherapy was regularly prescribed following surgery.
Fuadin.RTM., a trivalent antimonial agent, was an early product used to chemically treat heartworm in canines. It was determined, however, that while this drug proved effective at sterilizing female worms--thereby preventing the production of microfilariae, it was ineffective at destroying adult worms. This factor, in conjunction with demonstrated toxicity, caused this drug to fall out of common use.
Beginning in about 1970, levamisole became a drug thought to possess an adulticidal character. Extensive controlled studies, however, demonstrated that the adulticidal activity of the composition was widely inconsistent. On this basis, the only recommended use of levamisole in the treatment of dirofilaria immitis is as a microfilaricide. (See Levamisole in Dirofilariasis in Dogs, J.A.V.M.A. 176 (10 part 2), 1170-1172 (1980)).
Occurring simultaneously with the development of the surgical and chemical treatments thus discussed, was the development of a chemotherapy treatment with demonstrated and comparatively efficacious adulticidal character. Thiacetarsimide, a substituted phenyl arsenoxide, is available under several branded names including Caparsolate Sodium.RTM. and Filaramide.RTM.. In continuing studies dating back to 1947, thiacetarsimide has been shown to kill effective numbers of adult worms in canines when administered at a variety of dosage and frequency variables. Through continuous experimentation, the once standard fifteen (15) day treatment regimen which involved a once daily administration of 0.1 cc of a 1% thiacetarsimide solution per pound of canine body weight has now been supplanted by a regimen of twice daily administrations of the same solution (1% thiacetarsimide) in individual doses of 0.1 ml per pound of canine weight for two consecutive days. Despite established side-effects including anaphylactic shock and periodic mortality as well as known hepatotoxic and nephrotoxic potentials, this protocol continues to date as the only approved treatment of dirofilaria immitis due to its consistent adulticidal efficacy of greater than about 70 per cent. (See R. F. Jackson, et al., Proceedings of the Heartworm Symposium (1980), pages 137-138 and 153-156, Otto, Editor, Veterinary Medicine Publishing Company (1981) and Clarke E. Atkins, Heartworm Caval Syndrome, Current Veterinary Therapy XI--Small Animal Practice, pg. 725 W. B. Saunders Co., (1992)).
Recently, ivermectin and other avermectin compounds have developed as a group of antiparasiticidal compounds of microbial origin. Avermectins, generally, are disclosed in U.S. Pat. No. 4,310,519 to Albers-Schonberg, et. al. Therein, the applicability of this broad class of compounds is intimated in connection with canine heartworm disease and it is suggested at col. 14, lines 19-23 that a mixed concentrate of the compounds proved successful in treating microfilariae in a single dog. Significantly, however, no disclosure is made regarding the applicability of the avermectins, generally, or ivermectin, specifically, in the eradication of adult canine heartworms.
Ivermectin is disclosed in U.S. Pat. No. 4,199,569 to Chabala, et. al. As do Albers-Schonberg, et. al., this patent too only hints at the possible application of the avermectins and, more particularly, ivermectin, in treating heartworm disease in canines. Further, it too fails to disclose any method for treating adult heartworm-afflicted canines and, in fact, provides no disclosure regarding which aspect or stage of the disease may respond to any of the compounds therein disclosed.
More recently, and with reference to U.S. Pat. No. 4,430,329 to Blair, ivermectin has been more particularly disclosed in conjunction with the treatment of heartworm-afflicted canines. Specifically, a protocol has been disclosed which involves the initial, primary treatment of dirofilaria immitis with thiacetarsimide conventionally followed three to six weeks thereafter by treatment with ivermectin. While it is expressly noted at col. 2, lines 13-15 that "Ivermectin itself has no demonstrable activity against adult canine heartworm . . . ", and again at col. 4, line 5 that " . . . another drug [ivermectin] which has no adulticidal activity . . . ", ivermectin is therein disclosed and described as having a potentiating or synergistic effect on thiacetarsimide which, discretely, is known to have some activity against the adult heartworm. As such, it is believed that Blair teaches away from the method of the present invention which in no way employs thiacetarsimide.
U.S. Pat. No. 4,853,372 to Williams, et. al. discloses the most recent application of ivermectin as an antiparasiticidal composition--of which this inventor is aware. Specifically, this patent discloses an injectable ivermectin formulation which has demonstrated efficacy in treating ectoparasites such as ticks in cattle. In examples 1 and 2, at columns 3 and 4 respectively, two formulations are described. The first involves 1.0% weight by volume ivermectin in a solution of glycerol formal and propylene glycol and the second contains an equal concentration of ivermectin in a solution of water and propylene glycol. As with the other references hereto discussed, however, this patent also lacks any disclosure relating to the use of ivermectin as an adulticidal composition in the treatment of dirofilaria immitis.
The foregoing establishes that considerable, albeit unsuccessful efforts have been expended in this art to develop an effective, safe and convenient method for treating adult heartworms in canines. These efforts notwithstanding, the only known and approved modality existing presently requires the administration of thiacetarsimide, an arsenic-derived compound having a vast array of known side-effects and a demonstrated incidence of patient mortality. Thus, the art has lacked a safe, efficacious, convenient and comparably inexpensive method for killing adult heartworms in canines without using thiacetarsimide. The invention disclosed and claimed herein achieves these advantages in a manner not revealed by the prior art.